The aim of this proposal is to develop new culture techniques for the preparation and maintenance of adult human and mouse ganglia neurons specifically for the purpose of studying neuronal aging changes. The effects of various neurotropic agents (NGF, thyroid hormone, substance P, cyclic nucleotides and brain extract) on the adult neuron cultures will be analyzed, in order to determine whether these agents enhance the survival and regenerative capacity of isolated adult neurons in vitro. The genesis and basic properties of neurofibrillary tangles and lipofuscin granules, naturally occurring or experimentally induced, in cultured adult neurons will be analyzed. Attempts will be made to reproduce an in vitro model of the neuronl changes of Alzheimer's disease, i.e. paired helical filaments, in adult human neuron cultures.